Renal ammonia (NH3) buffer synthesis is critical to maintaining acid-base balance. Prostaglandins synthesized by the kidney play a critical role in modulating many vital renal functions including glomerular filtration rate, renal blood flow, and salt and water handling. The role of prostaglandins as modulators of ammoniagenesis has gone unstudied. Preliminary evidence from my laboratory strongly suggests that prostaglandins exert a tonic inhibitory effect on NH3 synthesis. I propose to evaluate the hypothesis that renal prostaglandins function as negative feedback inhibitors of ammoniagenesis. Accordingly, we will utilize in vivo clearances and balance techniques as well as in vitro techniques with renal cortical and medullary slices to study the interaction of PG and NH3 synthesis. Normal rats, rats receiving meclofenamate (PG inhibited rats) as well as rats receiving excess amounts of prostaglandins will be studied during various manipulation in systemic pH - a well-known modulator of ammonagenesis. I will determine if the effects of systemic pH on ammoniagenesis are mediated through alterations in prostaglandin synthesis. Finally the effects of prostaglandins on glutamine utilization for NH3 synthesis, both in vivo and in vitro, will be studied. Definition of the role of prostaglandin as modulators of ammoniagenesis will expand our understanding of the mechanisms by which the kidney regulates acid-base balance.